Urea transporters in kidney and erythrocytes

Sands, Jeff M.; Timmer, Richard T.; Gunn, Robert B.

doi:10.1152/ajprenal.1997.273.3.f321

Cited by 97 publications

(103 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The factors already known to influence urea transporter expression are those involved in the regulation of water or nitrogen excretion [13,15,36]. It is therefore interesting to compare the pathophysiological situation resulting from the metabolic derangements of diabetes with that induced by different concentrations of vasopressin or by alterations in protein intake.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-2 and urea transporter-A1 are up-regulated in rats with Type I diabetes mellitus

et al. 2001

View full text Add to dashboard Cite

In diabetes mellitus, water turnover in the body is enhanced because of the glucose-induced osmotic diuresis and it is usually assumed that the concentrating capacity of the kidney is partially impaired. On the other hand, plasma vasopressin concentration is known to be increased by several fold in patients with Type I (insulin-dependent) diabetes mellitus or Type II (non-insulin-dependent) diabetes mellitus as well as in animal models of experimental or genetic diabetes mellitus [1±6]. This high vasopressin concentration is accompanied by a desensitization of V1 a receptors in liver, kidney and platelets [7,8]. In contrast, renal V2 receptors, responsible for the antidiuretic action of the hormone, are not down-regulated [8].Actually, higher vasopressin in diabetes mellitus probably represents an appropriate adaptation by limiting to some extent the amount of water required Abstract Aims/hypothesis. Although the urine flow rate is considerably higher in diabetes mellitus, water reabsorption is greatly increased to concentrate an increased amount of solutes. Our study evaluated the expression of aquaporins and urea transporters, which are essential to the urinary concentration process. Methods. Northern blot and immunoblot were used to quantify mRNA and proteins for aquaporin-2 (AQP2) as well as urea transporters UT-A1, UT-A2 and UT-B1, in subzones of the renal medulla of rats with streptozotocin-induced diabetes. Results. In these rats, glycaemia, urine flow rate and water reabsorption were respectively fourfold, ninefold and fourfold those of control rats. The AQP2 protein isoforms were significantly up-regulated in outer and inner medulla. In the base and tip of inner medulla, UT-A1 mRNA was significantly up-regulated (three-and 1.3-fold, respectively) as well as the 117 kD protein (ten-and threefold, respectively) whereas the 97 kD protein was not changed or decreased twofold, respectively. This suggests that, in diabetes, the inner medullary collecting duct is endowed with more UT-A1, especially in its initial part. In the case of mRNA and proteins of UT-A2, located in thin descending limbs in the inner stripe of outer medulla, they were respectively not changed and down-regulated in diabetic rats. Conclusion/interpretation. This study shows that in diabetes, the increased expression of AQP2 and UT-A1 in medullary collecting duct is consistent with an improved concentrating activity. In addition, the underexpression of UT-A2 and the overexpression of UT-A1 in the initial medullary collecting duct are reminiscent of the changes seen after experimental reduction of urine concentration or low protein feeding. [Diabetologia (2001) 44: 637±645]

show abstract

Section: Discussionmentioning

confidence: 99%

Aquaporin-2 and urea transporter-A1 are up-regulated in rats with Type I diabetes mellitus

et al. 2001

View full text Add to dashboard Cite

show abstract

“…34 Conversely, investigations in Xenopus oocytes indicate that UT1, but not UT2, is regulated by the cAMP pathway. 34 In addition to UT1 and UT2, another facilitated urea transporter, first identified in erythropoietic tissue (UT3 or rUT-B1), has been localized in the descending vasa recta and contributes to the maintenance of the hypertonicity of the medulla. 35,36 Collecting Duct.…”

Section: Factors In the Control Of Water Excretionmentioning

confidence: 99%

Hyponatremia in cirrhosis: From pathogenesis to treatment†

et al. 1998

View full text Add to dashboard Cite

“…Rat UT3 has 62% amino acid identity to UT2 and is expressed strongly in kidney in descending vasa recta in the inner stripe of outer medulla, as well as in testis and brain (7,8). It is thought that these urea transporters have an important role in the urinary concentrating mechanism to establish a hypertonic renal medullary interstitium (9).…”

mentioning

confidence: 99%

“…These individuals are phenotypically grossly normal, but have a defect in their ability to produce a maximally concentrated urine (13). From the number of Kidd antigen proteins per erythrocyte and the erythrocyte urea permeability, it was estimated that the UT3 turnover rate is 2-15 ϫ 10 6 urea molecules/s (9,14). This turnover rate is substantially higher than that of usual solute carriers, suggesting a channel mechanism for urea transport.…”

mentioning

confidence: 99%

Urea Transporter UT3 Functions as an Efficient Water Channel

Yang

Verkman

1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

A family of molecular urea transporters (UTs) has been identified whose members appear to have an exceptionally high transport turnover rate. To test the hypothesis that urea transport involves passage through an aqueous channel, osmotic water permeability was measured in Xenopus oocytes expressing UTs. The UT3 class of urea transporters functioned as efficient water channels. Quantitative measurement of single channel water permeability ( p f ) using epitopetagged rat UTs gave p f (in cm 3 /s ؋ 10 ؊14 ) of 0.14 ؎ 0.11 (UT2) and 1.4 ؎ 0.2 (UT3), compared with 6.0 and 2.3 for water channels AQP1 and AQP3, respectively. Relative single channel urea permeabilities ( p urea ) were 1.0 (UT2), 0.44 (UT3), and 0.0 (AQP1). UT3-mediated water and urea transport were weakly temperature-dependent (activation energy <4 kcal/mol), inhibited > 75% by the urea transport inhibitor 1,3-dimethylthiourea, but not inhibited by the water transport inhibitor HgCl 2 . To test for a common water/urea pore, the urea reflection coefficient ( urea ) was measured by independent induced osmosis and solvent drag methods. In UT3-expressing oocytes, the time course of oocyte volume in response to different urea gradients (induced osmosis) gave urea ϳ0.3 for the UT3 pathway, in agreement with urea determined by the increase in uptake of [ 14 C]urea during osmotic gradient-induced oocyte swelling (solvent drag). In oocytes of comparable water and urea permeability coexpressing AQP1 (permeable to water, not urea) and UT2 (permeable to urea, not water), urea ‫؍‬ 1. These results indicate that UT3 functions as a urea/ water channel utilizing a common aqueous pathway. The water transporting function and low urea reflection coefficient of UT3 in vasa recta may be important for the formation of a concentrated urine by countercurrent exchange in the kidney. Several related urea transporters (UTs)1 have been cloned recently. The UT2 transporter (rat form referred to as rUT2, Ref. 1) was first identified in rabbit by expression cloning (2). The UT2 cDNA encodes a 397-amino acid glycoprotein that is expressed in the medullary portion of descending limbs of Henle in kidney (3, 4). UT1 is larger protein (929 amino acids) that contains the UT2 sequence at its C terminus fused to a 67% identical amino acid sequence at its N terminus (5). UT1 functions a cAMP-regulated urea transporter that is expressed at the apical membrane of inner medullary collecting duct cells. UT1 and UT2 are thought to be derived from a single gene by alternative splicing. A 391-amino acid urea transporter expressed in erythrocytes was initially cloned from human bone marrow (HUT11, Ref. 6) and subsequently from rat kidney (named UT3, Ref. 7). Rat UT3 has 62% amino acid identity to UT2 and is expressed strongly in kidney in descending vasa recta in the inner stripe of outer medulla, as well as in testis and brain (7,8). It is thought that these urea transporters have an important role in the urinary concentrating mechanism to establish a hypertonic renal medullary interstitium (9).UT3 ...

show abstract

Urea transporters in kidney and erythrocytes

Cited by 97 publications

References 0 publications

Aquaporin-2 and urea transporter-A1 are up-regulated in rats with Type I diabetes mellitus

Aquaporin-2 and urea transporter-A1 are up-regulated in rats with Type I diabetes mellitus

Hyponatremia in cirrhosis: From pathogenesis to treatment†

Urea Transporter UT3 Functions as an Efficient Water Channel

Contact Info

Product

Resources

About